Department of Biomedical Sciences and Collaborative Specialization in Neuroscience Program, University of Guelph, Guelph, ON N1G 2W1, Canada.
Int J Mol Sci. 2022 Dec 27;24(1):442. doi: 10.3390/ijms24010442.
Antioxidants are being explored as novel therapeutics for the treatment of neurodegenerative diseases such as Alzheimer's disease (AD) through strategies such as chemically linking antioxidants to synthesize novel co-drugs. The main objective of this study was to assess the cytoprotective effects of the novel antioxidant compound VANL-100 in a cellular model of beta-amyloid (Aβ)-induced toxicity. The cytotoxic effects of Aβ in the presence and absence of all antioxidant compounds were measured using the 3-(4,5-dimethylthiazol-2-yl)2-5-diphenyl-2H-tetrazolium bromide (MTT) assay in SH-SY5Y cells in both pre-treatment and co-treatment experiments. In pre-treatment experiments, VANL-100, or one of its parent compounds, naringenin (NAR), alpha-lipoic acid (ALA), or naringenin + alpha-lipoic acid (NAR + ALA), was administrated 24 h prior to an additional 24-h incubation with 20 μM non-fibril or fibril Aβ. Co-treatment experiments consisted of simultaneous treatment with Aβ and antioxidants. Pre-treatment and co-treatment with VANL-100 significantly attenuated Aβ-induced cell death. There were no significant differences between the protective effects of VANL-100, NAR, ALA, and NAR + ALA with either form of Aβ, or in the effect of VANL-100 between 24-h pre-treatment and co-treatment. These results demonstrate that the novel co-drug VANL-100 is capable of eliciting cytoprotective effects against Aβ-induced toxicity.
抗氧化剂作为一种新型治疗剂，正被探索用于治疗神经退行性疾病，如阿尔茨海默病（AD），通过将抗氧化剂与合成新型共药物的化学方法结合。本研究的主要目的是评估新型抗氧化剂化合物 VANL-100 在β-淀粉样蛋白（Aβ）诱导的毒性的细胞模型中的细胞保护作用。通过在 SH-SY5Y 细胞中进行 3-（4,5-二甲基噻唑-2-基）-2-5-二苯基-2H-四唑溴盐（MTT）测定，评估了在有或没有所有抗氧化剂化合物存在的情况下，Aβ的细胞毒性，在预处理和共处理实验中，VANL-100 或其母体化合物柚皮素（NAR）、α-硫辛酸（ALA）或柚皮素+α-硫辛酸（NAR+ALA），在与 20 μM 非纤维或纤维 Aβ孵育 24 小时之前，给予 24 小时预处理。共处理实验包括同时用 Aβ和抗氧化剂处理。VANL-100 的预处理和共处理显著减轻了 Aβ诱导的细胞死亡。VANL-100、NAR、ALA 和 NAR+ALA 与两种形式的 Aβ的保护作用之间，以及 VANL-100 在 24 小时预处理和共处理之间的作用，没有显著差异。这些结果表明，新型共药物 VANL-100 能够引发针对 Aβ诱导的毒性的细胞保护作用。
